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Suicide Gene Therapy

Prostate cancer is one of the most common cancers among older men. In 2012, the US alone reported around 2.7 million cases of prostate cancer. Fortunately, prostate cancer develops very slowly. In fact, the five-year survival rate in the US is nearly 99%. Prostate cancer also tends to develop very late in life, meaning treatment is often not necessary. However, aggressive forms of prostate cancer still exist that need proper treatment.

In a recent study, researchers at the Houston Methodist Hospital tested out a new method for treating prostate cancer in human patients, and the results looked very promising. Their unique treatment scheme employs a drug commonly used against the herpes virus, valaciclovir, in a clever way to target tumor cells.

To key to how valaciclovir works against herpes virus is that the virus-made enzyme, thymidine kinase (TK), readily converts the drug into a fake DNA nucleotide. When the virus incorporates this fake nucleotide into its own replication machinery, the machinery then breaks down and the virus is no longer able to replicate. Though TK is also found in normal cells, the viral form of this enzyme is about 1,000 times more efficient at converting valaciclovir into fake nucleotide, meaning this chemical conversion really only occurs in virus-infected cells.

For their study, Houston Methodist Hospital researchers took the viral gene that codes for TK, and attached it to a different virus (adenovirus) that is good at transferring genetic material into cells. Researchers then injected this new virus directly into the cancerous tumor, effectively transferring the viral TK gene into tumor cells and causing them to produce the enzyme. When the cancer patient is then given valaciclovir, the same events that occur in a herpes-infected cell will now occur in the tumor cells. That is, the viral TK enzyme within the infected tumor cells converts valaciclovir into a fake DNA nucleotide, interrupting the cell’s replication machinery and preventing it from replicating. The researchers call their treatment scheme “suicide gene therapy”.

The great news is that suicide gene therapy appears generally safe, given that the patients did not experience too many adverse effects. The only real concern was that nearly one-third of the patients developed a slight fever during therapy. However, more human trials are necessary before the FDA can approve this drug. This experiment was only considered a Phase II clinical trial, meaning it must still go through Phase III trials. During this phase, researchers will test the treatment against the current gold-standard treatment for prostate cancer to see if it actually outperforms.

Whether or not suicide gene therapy makes it to market will be interesting to watch. The important thing here is that it’s not “just another drug”, it’s a new, unique way of utilizing drugs to combat cancer. Should the drug make it to market, this would provide a proof of principal for using suicide gene therapy to combat disease in general, a feat that scientists have yet to achieve.